We hypothesized that gabapentin may be effective in the treatment of hyperemesis gravidarum (HG) based on previous experience we had associating gabapentin with marked reductions in refractory nausea and vomiting in other patient populations. Based on pregnancy registry data, there does not appear to be any contraindication to gabapentin use during pregnancy. We recently published the results of our open-label study using gabapentin among 7 HG patients, which showed an 80% and 94% reduction in mean nausea and emesis, respectively, after 2 weeks of gabapentin therapy and a >3x increase in mean nausea and a >7x increase in mean emesis within 2 days after gabapentin was discontinued. We now propose a randomized, double-blind, 2-arm clinical trial to compare the efficacy and tolerability of gabapentin to ondansetron in the treatment of HG. Eligible subjects will have moderate- severe refractory nausea and emesis of onset before 16 weeks gestation causing >5% weight loss from pre-pregnancy weight or 3-4+ ketonuria. Eighty (80) HG participants will be equally randomized to each of the 2 groups for 2 weeks and then open-label gabapentin with prn ondansetron will be provided for subjects for as long as needed. Subjects will be enrolled at the University at Buffalo and the University of Rochester. The Primary Outcome Measure will be the mean inter-period difference in the percent change from Baseline to the Study Endpoint in mean daily Motherisk-PUQE scores (a validated nausea and emesis diary of pregnancy). A flexible Study Endpoint will be used in order to focus assessment of the Primary Outcome Measure in the outpatient setting prior to subjects receiving iv hydration, which is when HG symptoms typically are most severe and refractory to treatment. The Study Endpoint will either be the mean values from Days 13-14 or, for subjects requiring repeat iv hydration after hospital discharge, it will be the mean values from the 48 hours prior to this repeat iv hydration administration. HG inpatients are typically discharged after 2-5 days, which will provide ample time in the outpatient setting prior to the Study Endpoint. Secondary outcomes will include oral nutrition, quality of life, global satisfaction, blood laboratory values, need for iv hydration or hospital admission, and maternal and fetal outcome assessments.